Diabetes is a series of metabolic disorders syndrome induced by factors such as body islet dysfunction and insulin resistance. Multiple pathogenic factors such as genetic factors, immune dysfunction, and mental factors can cause diabetes. According to the World Health Organization statistics, by 2011, there are about 346 million people suffering from diabetes. In 2004, about 3.4 million people died of high blood sugar, and more than 80% of diabetes deaths occur in low- and middle-income countries.
There are now many drugs for the treatment of type II diabetes, including metformin, sulfonylureas, DPP-4 inhibitors, PPARγ agonists, α-glucosidase inhibitors, insulin and GLP-1 analogues. However, the existing medicines have certain problems such as no significant effect, short duration time. Some drugs even have side effects such as hypoglycemia, weight gain, edema, fractures, lactic acidosis and gastrointestinal discomfort.
Adenosine monophosphate activated protein kinase (AMPK) plays an important role in metabolism of glucose and lipid in vivo. It is an energy meter and metabolic main switch reflecting the change of intracellular energy state. Its activation can significantly improve metabolism of glucose and lipid in type 2 diabetes, enhance activity of insulin sensitivity, and has been confirmed as a new target for treatment of type 2 diabetes. Studies have shown that many known drugs or natural products for treatment of type 2 diabetes have been found to indirectly activate AMPK in vivo, and the therapeutic effect may be partially due to activation of AMPK, but these indirect activators have side effects such as gastrointestinal discomfort and weight gain. Therefore, it will be an effective way to find treatment for type II diabetes by finding and discovering small molecule activators of AMPK, especially small molecule activators directly acting on AMPK.
Therefore, there is an urgent need to provide novel AMPK activators with less side effects.